Process for the preparation of glycosyl azides

Abstract

A process for stereospecific preparation of glycosyl azides by reacting a metal azide with a glycosyl phosphate triester having the phosphate group cis to the adjacent C-2 substituent is disclosed.

What is claimed is: 
     
       1. A process for the stereospecific preparation of a glycosyl azide of Formula III or IV ##STR6## wherein: R is alkyl, aryl, aralkyl, acyl or aroyl; X is oxygen or NH; when X is oxygen, R 2  is alkyl, aryl, aralkyl, acyl or aroyl; when X is NH, R 2  is acyl, aroyl, or alkylcarbamyl; and   one of Z 1  or Z 2  is N 3 , and the other is H; comprising reacting a metal azide with a glycosyl phosphate triester having the phosphate group cis to the adjacent C-2 substituent at a temperature of from about 40 degrees Centigrade to about 80 degrees Centigrade wherein the glycosyl phosphate triester is a compound of Formula I or II ##STR7## wherein: R is alkyl, aryl, aralkyl, acyl or aroyl;     X is oxygen or NH; when X is oxygen R 2  is alkyl, aryl, aralkyl, acyl or aroyl, when X is NH, R 2  is acyl, aroyl, or alkylcarbamyl;   one of Y 1  or Y 2  is O--P↑O(OR 4 ) 2   and the other is H; and     R 4  is aryl and wherein the reaction is carried out in the presence of a polar, aprotic solvent.     
     
     
       2. The process of claim 1 wherein for Formula III or IV: R is benzyl, acetyl or benzoyl;   When X is oxygen, R 2  is benzyl, acetyl or benzoyl;   When X is -NH, R 2  is acetyl;   one of Z 1  or Z 2  is N 3 , and the other is hydrogen.   
     
     
       3. The process of claim 1 wherein for Formula I or II: R is benzyl, acetyl or benzoyl;   When X is oxygen, R 2  is benzyl, acetyl, or benzoyl;   When X is -NH, R 2  is acetyl;   one of Y 1  or Y 2  is ##STR8##  and the other is H; and R 4  is phenyl.   
     
     
       4. The process of claim 1 wherein the metal azide is an alkali metal azide. 
     
     
       5. The process of claim 4 wherein the metal azide is sodium azide or potassium azide. 
     
     
       6. The process of claim 1 conducted at a temperature of from about 50° C. to about 70° C. 
     
     
       7. The process of claim 1 wherein the solvent is selected from the group consisting of dimethylformamide, dimethylacetamide, dimethylsulfoxide, dimethylcarbonate, and N-methylpyrrolidone. 
     
     
       8. The process of claim 1 wherein the mole ratio of glycosyl phosphate triester to metal azide is from about 1:1 to about 1:10. 
     
     
       9. The process of claim 1 conducted in a dry inert atmosphere of nitrogen or argon. 
     
     
       10. The process of claim 1 conducted with vigorous agitation.